Early HIV Treatment Restores Immune System

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Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Note that this prospective cohort study demonstrated superior HIV control and CD4 counts among patient initiated on HIV therapy prior to achieving CD4 counts <500/mm3 -- adding to the potential value of earlier initiation of therapy.

Be aware that the study findings may reflect inherent differences between those with higher baseline CD4 counts and those with lower baseline CD4 counts as it lacked an adequate control group.

KUALA LUMPUR -- Antiretroviral therapy can restore aspects of a normal immune system in some patients with chronic HIV, as well as reduce the size of the viral reservoir, a researcher said here.

The catch is they have to start with a relatively intact immune system, with at least 500 CD4-positive T cells per microliter of blood, according to Laurent Hocqueloux, MD, of the Centre Hospitalier Régional in Orleans, France.

But the finding, from a prospective observational cohort study, suggests such patients might be most likely to benefit from future interventional trials aimed at eradicating the virus, Hocqueloux argued at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention.

Hocqueloux and colleagues have previously shown that treatment early in HIV infection leads to a weak viral reservoir and a good restoration of the immune system.

In some patients treated very early, that has led to what the researchers are calling "post-treatment control" -- the ability to go off HIV therapy without having the virus resume growing in the body.

But, Hocqueloux said, they wondered if some patients who had reached what is considered chronic infection might also see immune restoration and a weak viral reservoir.

To find out, they studied 309 patients treated with antiretroviral drugs from 2005 through 2012 and asked what proportion would regain a normal CD4 count of at least 900 cells, a normal ratio of CD4 to CD8 cells of more than 1.0, and fewer than 2.3 log10 copies of HIV DNA per million peripheral blood mononuclear cells (PBMCs).

Patients were stratified by their lowest CD4 count before starting therapy -- fewer than 200, 200 to 499, and 500 or more.

At study entry, Hocqueloux reported none of the patients met the primary endpoint.

But after 4 years of treatment, 30% of those who started with more than 500 cells did so, compared with 7% of those in the middle category, and 2% of those in the lowest group. The trend was significant at P=0.0001.

Patients who started with 500 of more CD4 cells wound up with a median count of 1,100 cells, a CD4/CD8 ratio of 1.25, and an HIV DNA load of 2.51 log10 copies per million PBMCs.

Those who started with fewer than 500 cells were significantly worse on all three benchmarks, Hocqueloux said.

He cautioned that the study had a cohort design, had short follow-up, and still needs to be confirmed in other cohorts.

But at a minimum, the study confirms the value of early treatment, before the immune system is too badly degraded, he said. And the findings may point toward good candidates for trials of therapeutic vaccines or strategies aimed at "emptying" the viral reservoir and leading to remission.

Indeed, the study found a "very dramatic difference" between those with high and low initial CD4 counts in terms of the outcome of therapy, commented Robert Murphy, MD, of Northwestern University Feinberg School of Medicine in Chicago.

But patients who met the study's endpoint are unlikely to be able to control the virus on their own, without the aid of HIV therapy, because they are already chronically infected, Murphy told MedPage Today.

Still, he agreed with Hocqueloux that they might be the best choices for proof-of-concept studies aimed eradicating the viral reservoir, he said. "To prove the concept," he said, "you have to pick the patients most likely to succeed and these are those patients."

For that reason, he added, "this is a really, really important study."

The study was supported by the French national AIDS research agency. Hocqueloux did not make any financial disclosures.

Murphy reported financial links with Gilead.

Reviewed by F. Perry Wilson, MD, MSCE Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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